Green tea contains astringent tea tannin in an amount of 10% to 15%. Tea tannin is comprised of polyphenols which are catechins represented by epigallocatechin-3-gallate(EGCG), epigallocatechin(EGC), epicatechin-3-gallate(ECG), epicatechin(EC), gallocatechin-3-gallate(GCG), gallocatechin(GC) and catechin(C).
Catechins have been reported to have: peroxy-lipid-inhibiting activity(Kinura et al., J. Jpn. Soc. Nutr. Food Sci., 37, 223-232 (1984)); antioxidant activity for fat and fatty oil(Okuda, T. et al., Chem. Pharmacol. Bull., 31, 1625-1631 (1983)); antihypertensive activity; antifungal activity; antihyperglycemic activity; hypercholesteremia-inhibiting activity; antiulcerative activity; and anticancer activity(Fukuyo, M. et al., J. Jpn. Soc. Nutr. Food Sci., 39, 495-500 (1986)).
Percutaneous transluminal coronary angioplasty (PTCA) has been widely practiced for treating ischemic cardiac diseases. However, post-PTCA coronary restenosis occurs at an unacceptably high frequency of 30% to 50% (Popma, J. J. et al., Circulation, 84, 1426-1436 (1991); and Gruentzig, A. R. et al., N Engl J Med, 316, 1127-1132 (1987)).
According to the clinical and experimental studies, restenosis proceeds via the steps of: elastic recoiling; thrombogenesis and organization of the connective tissue; intimal hyperplasia; and vessel wall remodeling(Mintz, G. S. et al., Circulation, 94, 35-43 (1996); Kagan, S. A., Surg Clin North Am, 78, 481-500 (1998); McBride, W. et al., N Engl J Med, 318, 1734-1737 (1988); Califf, R. M. et al., J Am Coll Cardiol, 17, 2B-13B (1991); Schwartz, S. M. et al., Mayo Clin Proc, 68, 54-62 (1993); and Schwartz, R. S. et al., Mayo Clin Proc, 68, 54-62 (1993)). The intimal hyperplasia, in particular, is caused by the growth and movement of vascular smooth muscle cells(VSMCs) coupled with the formation of an extracellular matrix, the VSMCs being induced by the combined actions of materials released from damaged blood vessels and growth-stimulating materials produced by the activated platelet.
It has been reported that stent enthesis into the coronary artery effectively prevents elastic recoil and vessel wall remodeling, thereby lowering the frequency of restenosis to about 10%(Serruys, P. W. et al., N Engl J Med, 331, 496-501 (1988); and Fischman, D. L. et al., N Engl J Med, 331, 496-501 (1994)). However, the stent enthesis may promote a serious case of intimal hyperplasia, to thereby generate in-stent restenosis.
To prevent coronary restenosis, therefore, various attempts have made using advanced PTCA equipment, e.g., atherectomy, angioplasty using a laser, rotablator, angioplasty of the coronary vessel using a cutting balloon, and irradiative treatments. Further, systemic or local drug therapies have been attempted using an antiplatelet agent, an antithrombotic agent, a vasodilator, a cytostatic, a lipid metabolism-improving agent or an antioxidant(Califf, R. M. et al., J Am Coll Cardiol, 17, 2B-13B (1991); Popma, J. J. et al., Circulation, 84, 1426-1436 (1991); and Herrman, J. P. R. et al., Drugs, 46, 18-22 (1991)); and also attempts have been made to employ a gene therapy(De Young, M. B. et al., Circ Res, 82, 306-313 (1998); Baek, S. H. et al., Circ Res, 82, 295-305 (1998); Libby, P., Circ Res, 82, 404-406 (1998); Nikol, S., Heart, 78, 426-428 (1997); Morishita, R. et al., Circ Res, 82, 1023-1028 (1998); and George, S. J. et al., Hum Gene Ther, 9, 867-877 (1998)). Among these, the systemic drug therapy, which was found to be effective in animal tests, has failed to prevent coronary restenosis in clinical tests due to the occurrence of undesirable side effects. As restenosis occurs at a local PTCA site of coronary artery, a local drug therapy which delivers a high concentration of a drug to the site is more desirable than a systemic drug therapy. For such a local drug delivery, there have recently been developed various methods employing such devices as a double balloon catheter, a dispatch, a microporous balloon(Brieger D. et al., Cardiovasc Res, 35, 405-413 (1997); Yla-Herttuala S., Curr Opin Lipidol, 8, 72-76 (1997); and Laitinen, M. et al., Pharmacol Res, 37, 251-254 (1998)), a slow-release microsphere and a drug-coated stent. However, these methods are limited in their effectiveness. Therefore, there has existed a need to develop an effective method for preventing coronary restenosis after PTCA.